Zinc oxide nanoparticles exhibit cytotoxicity and genotoxicity through oxidative stress responses in human lung fibroblasts and Drosophila melanogaster

Cheng Teng Ng,1,2,* Liang Qing Yong,1,* Manoor Prakash Hande,3 Choon Nam Ong,2 Liya E Yu,4 Boon Huat Bay,1 Gyeong Hun Baeg1 1Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; 2Environmental Research Institute, National University of Singapore, Sing...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Ng CT, Yong LQ, Hande MP, Ong CN, Yu LE, Bay BH, Baeg GH
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	zinc oxide nanoparticles ROS oxidative stress MRC5 cells Drosophila Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/52913dd4660f446993b1987d5f023086
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:52913dd4660f446993b1987d5f023086
record_format	dspace
spelling	oai:doaj.org-article:52913dd4660f446993b1987d5f0230862021-12-02T04:58:03ZZinc oxide nanoparticles exhibit cytotoxicity and genotoxicity through oxidative stress responses in human lung fibroblasts and Drosophila melanogaster1178-2013https://doaj.org/article/52913dd4660f446993b1987d5f0230862017-02-01T00:00:00Zhttps://www.dovepress.com/zinc-oxide-nanoparticles-exhibit-cytotoxicity-and-genotoxicity-through-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Cheng Teng Ng,1,2,* Liang Qing Yong,1,* Manoor Prakash Hande,3 Choon Nam Ong,2 Liya E Yu,4 Boon Huat Bay,1 Gyeong Hun Baeg1 1Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; 2Environmental Research Institute, National University of Singapore, Singapore; 3Department of Physiology, Yong Loo Lin School of Medicine, 4Department of Civil and Environmental Engineering, National University of Singapore, Singapore, Singapore *These authors contributed equally to this work Background: Although zinc oxide nanoparticles (ZnO NPs) have been widely used, there has been an increasing number of reports on the toxicity of ZnO NPs. However, study on the underlying mechanisms under in vivo conditions is insufficient.Methods: In this study, we investigated the toxicological profiles of ZnO NPs in MRC5 human lung fibroblasts in vitro and in an in vivo model using the fruit fly Drosophila melanogaster. A comprehensive study was conducted to evaluate the uptake, cytotoxicity, reactive oxygen species (ROS) formation, gene expression profiling and genotoxicity induced by ZnO NPs.Results: For in vitro toxicity, the results showed that there was a significant release of extracellular lactate dehydrogenase and decreased cell viability in ZnO NP-treated MRC5 lung cells, indicating cellular damage and cytotoxicity. Generation of ROS was observed to be related to significant expression of DNA Damage Inducible Transcript (DDIT3) and endoplasmic reticulum (ER) to nucleus signaling 1 (ERN1) genes, which are ER stress-related genes. Oxidative stress induced DNA damage was further verified by a significant release of DNA oxidation product, 8-hydroxydeoxyguanosine (8-OHdG), as well as by the Comet assay. For the in vivo study using the fruit fly D. melanogaster as a model, significant toxicity was observed in F1 progenies upon ingestion of ZnO NPs. ZnO NPs induced significant decrease in the egg-to-adult viability of the flies. We further showed that the decreased viability is closely associated with ROS induction by ZnO NPs. Removal of one copy of the D. melanogaster Nrf2 alleles further decreased the ZnO NPs-induced lethality due to increased production of ROS, indicating that nuclear factor E2-related factor 2 (Nrf2) plays important role in ZnO NPs-mediated ROS production.Conclusion: The present study suggests that ZnO NPs induced significant oxidative stress-related cytotoxicity and genotoxicity in human lung fibroblasts in vitro and in D. melanogaster in vivo. More extensive studies would be needed to verify the safety issues related to increased usage of ZnO NPs by consumers. Keywords: zinc oxide nanoparticles, ROS, oxidative stress, MRC5 cells, Drosophila Ng CTYong LQHande MPOng CNYu LEBay BHBaeg GHDove Medical Pressarticlezinc oxide nanoparticlesROSoxidative stressMRC5 cellsDrosophilaMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 1621-1637 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	zinc oxide nanoparticles ROS oxidative stress MRC5 cells Drosophila Medicine (General) R5-920
spellingShingle	zinc oxide nanoparticles ROS oxidative stress MRC5 cells Drosophila Medicine (General) R5-920 Ng CT Yong LQ Hande MP Ong CN Yu LE Bay BH Baeg GH Zinc oxide nanoparticles exhibit cytotoxicity and genotoxicity through oxidative stress responses in human lung fibroblasts and Drosophila melanogaster
description	Cheng Teng Ng,1,2,* Liang Qing Yong,1,* Manoor Prakash Hande,3 Choon Nam Ong,2 Liya E Yu,4 Boon Huat Bay,1 Gyeong Hun Baeg1 1Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; 2Environmental Research Institute, National University of Singapore, Singapore; 3Department of Physiology, Yong Loo Lin School of Medicine, 4Department of Civil and Environmental Engineering, National University of Singapore, Singapore, Singapore *These authors contributed equally to this work Background: Although zinc oxide nanoparticles (ZnO NPs) have been widely used, there has been an increasing number of reports on the toxicity of ZnO NPs. However, study on the underlying mechanisms under in vivo conditions is insufficient.Methods: In this study, we investigated the toxicological profiles of ZnO NPs in MRC5 human lung fibroblasts in vitro and in an in vivo model using the fruit fly Drosophila melanogaster. A comprehensive study was conducted to evaluate the uptake, cytotoxicity, reactive oxygen species (ROS) formation, gene expression profiling and genotoxicity induced by ZnO NPs.Results: For in vitro toxicity, the results showed that there was a significant release of extracellular lactate dehydrogenase and decreased cell viability in ZnO NP-treated MRC5 lung cells, indicating cellular damage and cytotoxicity. Generation of ROS was observed to be related to significant expression of DNA Damage Inducible Transcript (DDIT3) and endoplasmic reticulum (ER) to nucleus signaling 1 (ERN1) genes, which are ER stress-related genes. Oxidative stress induced DNA damage was further verified by a significant release of DNA oxidation product, 8-hydroxydeoxyguanosine (8-OHdG), as well as by the Comet assay. For the in vivo study using the fruit fly D. melanogaster as a model, significant toxicity was observed in F1 progenies upon ingestion of ZnO NPs. ZnO NPs induced significant decrease in the egg-to-adult viability of the flies. We further showed that the decreased viability is closely associated with ROS induction by ZnO NPs. Removal of one copy of the D. melanogaster Nrf2 alleles further decreased the ZnO NPs-induced lethality due to increased production of ROS, indicating that nuclear factor E2-related factor 2 (Nrf2) plays important role in ZnO NPs-mediated ROS production.Conclusion: The present study suggests that ZnO NPs induced significant oxidative stress-related cytotoxicity and genotoxicity in human lung fibroblasts in vitro and in D. melanogaster in vivo. More extensive studies would be needed to verify the safety issues related to increased usage of ZnO NPs by consumers. Keywords: zinc oxide nanoparticles, ROS, oxidative stress, MRC5 cells, Drosophila
format	article
author	Ng CT Yong LQ Hande MP Ong CN Yu LE Bay BH Baeg GH
author_facet	Ng CT Yong LQ Hande MP Ong CN Yu LE Bay BH Baeg GH
author_sort	Ng CT
title	Zinc oxide nanoparticles exhibit cytotoxicity and genotoxicity through oxidative stress responses in human lung fibroblasts and Drosophila melanogaster
title_short	Zinc oxide nanoparticles exhibit cytotoxicity and genotoxicity through oxidative stress responses in human lung fibroblasts and Drosophila melanogaster
title_full	Zinc oxide nanoparticles exhibit cytotoxicity and genotoxicity through oxidative stress responses in human lung fibroblasts and Drosophila melanogaster
title_fullStr	Zinc oxide nanoparticles exhibit cytotoxicity and genotoxicity through oxidative stress responses in human lung fibroblasts and Drosophila melanogaster
title_full_unstemmed	Zinc oxide nanoparticles exhibit cytotoxicity and genotoxicity through oxidative stress responses in human lung fibroblasts and Drosophila melanogaster
title_sort	zinc oxide nanoparticles exhibit cytotoxicity and genotoxicity through oxidative stress responses in human lung fibroblasts and drosophila melanogaster
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/52913dd4660f446993b1987d5f023086
work_keys_str_mv	AT ngct zincoxidenanoparticlesexhibitcytotoxicityandgenotoxicitythroughoxidativestressresponsesinhumanlungfibroblastsanddrosophilamelanogaster AT yonglq zincoxidenanoparticlesexhibitcytotoxicityandgenotoxicitythroughoxidativestressresponsesinhumanlungfibroblastsanddrosophilamelanogaster AT handemp zincoxidenanoparticlesexhibitcytotoxicityandgenotoxicitythroughoxidativestressresponsesinhumanlungfibroblastsanddrosophilamelanogaster AT ongcn zincoxidenanoparticlesexhibitcytotoxicityandgenotoxicitythroughoxidativestressresponsesinhumanlungfibroblastsanddrosophilamelanogaster AT yule zincoxidenanoparticlesexhibitcytotoxicityandgenotoxicitythroughoxidativestressresponsesinhumanlungfibroblastsanddrosophilamelanogaster AT baybh zincoxidenanoparticlesexhibitcytotoxicityandgenotoxicitythroughoxidativestressresponsesinhumanlungfibroblastsanddrosophilamelanogaster AT baeggh zincoxidenanoparticlesexhibitcytotoxicityandgenotoxicitythroughoxidativestressresponsesinhumanlungfibroblastsanddrosophilamelanogaster
_version_	1718400948480507904

Zinc oxide nanoparticles exhibit cytotoxicity and genotoxicity through oxidative stress responses in human lung fibroblasts and Drosophila melanogaster

Ejemplares similares